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曲克芦丁负载羧甲基纤维素/硅磷酸钙骨水泥复合骨水泥的制备及其成骨性能研究

Preparation and osteogenic performance study of troxerutin-loaded carboxymethyl cellulose/Si-calcium phosphate cement composite bone cement.

作者信息

Wei Jintao, Liu Jianshen, Wu Jianxing, Chen Yan, Wei Kunhua, Guo Jiao, Su Zhengquan

机构信息

Guangdong Engineering Research Center of Natural Products and New Drugs, Guangdong Provincial University Engineering Technology Research Center of Natural Products and Drugs, Guangdong Pharmaceutical University, Guangzhou 510006, China; Guangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine, Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education of China, Guangdong TCM Key Laboratory for Metabolic Diseases, Guangdong Pharmaceutical University, Guangzhou 510006, China.

Key Laboratory of State Administration of Traditional Chinese Medicine for Production & Development of Cantonese Medicinal Materials, Guangzhou Comprehensive Experimental Station of National Industrial Technology System for Chinese Materia Medica, Guangdong Engineering Research Center of Good Agricultural Practice & Comprehensive Development for Cantonese Medicinal Materials, School of Chinese Materia Medica, Guangdong Pharmaceutical University, Guangzhou 510006, China.

出版信息

Biomater Adv. 2025 Dec;177:214434. doi: 10.1016/j.bioadv.2025.214434. Epub 2025 Jul 28.

DOI:10.1016/j.bioadv.2025.214434
PMID:40749384
Abstract

Bone defects from trauma, infection, and tumour resection are a growing clinical challenge due to global population aging. Current treatments like autologous and allogeneic bone grafting have limitations. This study focused on optimizing ion-doped α-tricalcium phosphate (α-TCP) preparation and developing calcium phosphate cement (CPC) with superior physicochemical and biological properties. Calcium pyrophosphate (CPP) and calcium carbonate (CaCO₃) showed the highest conversion efficiency during synthesis. Adding SiO₂ to this combination generated high-purity silicon-doped α-TCP (Si-α-TCP) powder at 1200 °C. To enhance CPC's performance, different amounts of sodium carboxymethyl cellulose (CMC) were added to the setting liquid. The CMC/Si-CPC with 1 %wt CMC demonstrated the best physicochemical properties, with improved setting time, compressive strength, injectability, and anti-dispersion. In drug-loading experiments, CMC promoted the release of Troxerutin (TRO), showing burst release within 6 h followed by sustained release. In vitro experiments with MC3T3-E1 cells confirmed good biocompatibility and osteogenic activity, further enhanced by Si-ion doping and 0.5 mg/mL TRO in the setting liquid. In vivo experiments, including rat subcutaneous and rabbit femoral defect implantation, confirmed effective osteoconductivity and osseointegration without inflammation or necrosis. In conclusion, this study successfully prepared high-purity Si-α-TCP powder by optimizing raw material combinations and Si-ion doping. CMC improved CPC's physicochemical properties, while Si-ion doping and TRO loading enhanced its biocompatibility and osteogenic activity. TRO/CMC/Si-CPC is promising for bone defect treatment and offers a new concept for bone tissue engineering materials.

摘要

由于全球人口老龄化,创伤、感染和肿瘤切除导致的骨缺损成为日益严峻的临床挑战。目前的治疗方法,如自体骨移植和异体骨移植,都存在局限性。本研究聚焦于优化离子掺杂α - 磷酸三钙(α-TCP)的制备,并开发具有优异物理化学和生物学性能的磷酸钙骨水泥(CPC)。焦磷酸钙(CPP)和碳酸钙(CaCO₃)在合成过程中显示出最高的转化效率。向该组合中添加SiO₂可在1200°C下生成高纯度硅掺杂α-TCP(Si-α-TCP)粉末。为提高CPC的性能,在固化液中添加了不同量的羧甲基纤维素钠(CMC)。含1%wt CMC的CMC/Si-CPC表现出最佳的物理化学性能,其凝固时间、抗压强度、可注射性和抗分散性均有所改善。在载药实验中,CMC促进了曲克芦丁(TRO)的释放,在6小时内呈现突释,随后持续释放。用MC3T3-E1细胞进行的体外实验证实了良好的生物相容性和成骨活性,固化液中的Si离子掺杂和0.5mg/mL TRO进一步增强了这些性能。体内实验,包括大鼠皮下和兔股骨缺损植入实验,证实了有效的骨传导性和骨整合,且无炎症或坏死。总之,本研究通过优化原料组合和Si离子掺杂成功制备了高纯度Si-α-TCP粉末。CMC改善了CPC的物理化学性能,而Si离子掺杂和TRO负载增强了其生物相容性和成骨活性。TRO/CMC/Si-CPC在骨缺损治疗方面具有潜力,并为骨组织工程材料提供了新的概念。

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